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Nadal

Fakultäten » Medizinische Fakultät » Kinderspital Zürich: Medizinische Klinik » Infektiologie, Abteilung » Prof. Dr. David Nadal » Nadal

Completed research project

Title / Titel Contribution of microbial stimulation of Toll-like receptor (TLR)9 to the formation of Epstein-Barr virus (EBV)-associated tumours
PDF Abstract (PDF, 14 KB)
Summary / Zusammenfassung This project aims to test our hypothesis that stimulation by microbial antigens, as occurs in daily life, contributes to tumour formation of EBV-containing B lymphocytes. This depends on the gene expression of Toll-like receptors (TLRs), the pathogen/pattern-recognition machinery of the innate immune system, and of associated cytokines. We will infect cord blood leukocytes, which are naturally devoid of memory cells or peripheral blood leukocytes from healthy EBV carriers, in the presence or absence of exogenous immunosuppression, with EBV. To create conditions of immunosuppression, cyclosporin A (CsA), which is used in transplant recipients, will be added to the cell culture medium. Subsequently, we will quantitatively assess the expression of EBV genes and host genes encoding TLR9 and cytokines, respectively, in the presence of naive (inexperienced) versus experienced adaptive immunity. Gene expression will be assessed employing real-time polymerase chain reaction assays recently developed in our laboratory. Furthermore, we will elucidate the dynamics of gene expression, details of the virus-host interaction, and the key steps fuelling tumour formation. In analogy to natural daily exposure to environmental antigens, CpG oligideoxynucelotides (ODNs) will be used to stimulate TLR9 in different immune conditions, to define their potential role in the formation of EBV-harbouring tumours.
Project leadership and contacts /
Projektleitung und Kontakte
Prof. Dr. med. David Nadal (Project Leader) david.nadal@kispi.uzh.ch
PD Dr. med. Roger Lauener roger.lauener@kispi.uzh.ch
Funding source(s) /
Unterstützt durch
Foundation
Krebsliga Kanton Zürich
Duration of Project / Projektdauer Aug 2004 to Jul 2005